Lung cancer is the second most common cancer in the United States, but high recurrence rates persist for patients with early-stage disease. A recent study published by Black et al in Nature Medicine has found that even very low traces of circulating tumor DNA (ctDNA) may be linked to increased recurrence risk in patients with early-stage lung adenocarcinoma, suggesting a potential role for more sensitive personalized genomic tests to guide treatment.
The findings, based on an analysis of the TRACERx study, showed that the presence of ctDNA was associated with worse clinical outcomes in lung adenocarcinoma, and patients with < 80 ppm preoperative ctDNA levels experienced reduced overall survival compared with ctDNA-negative patients.
Study Details
In this study, a highly sensitive genomic test—NeXT Personal—was used to analyze preoperative blood samples from a TRACERx cohort of 171 patients with early-stage non–small cell lung cancer (NSCLC). NeXT Personal uses whole-genome sequencing of a patient’s tumor to identify a unique signature of up to approximately 1,800 variants. The assay has been analytically validated to detect ctDNA at 1 to 3 ppm of ctDNA with 99.9% specificity.
The test showed high sensitivity for detecting stage I to III NSCLC preoperatively, including 100% of nonadenocarcinomas and 81% of lung adenocarcinomas, a common subtype that has previously been one of the most challenging to detect in blood samples because of low ctDNA shedding.
The investigators found that ctDNA levels prior to surgery were highly prognostic for overall survival in patients with early-stage lung adenocarcinoma. Patients who tested negative for ctDNA with NeXT Personal prior to surgery exhibited a 5-year overall survival rate of 100%, whereas patients testing positive had a high overall risk of relapse during that same period. Furthermore, patients who tested positive for very low traces of cancer (< 80 ppm of ctDNA) still had a high risk of recurrence, suggesting the importance of ultrasensitive measurable residual disease testing.
“This study demonstrates the potential of using more sensitive ctDNA tests like NeXT Personal in detecting lung cancer. These tools are important for personalizing care and maximizing the clinical benefit for individual patients,” said study author Charles Swanton FRCP, BSc, PhD, of The Francis Crick Institute in London.
